There is a growing body of information that viruses play a vital role in a broad range of diseases, some of which represent the most serious of man's ills. Arthritis, juvenile arthritis, diabetes, Hodgkin's disease, and various immunological diseases and degenerative diseases of the central nervous system have been linked with viruses as the causative agent.
At present, the control of virus infections is primarily achieved by means of immunization vaccines. For example, poliomyelitis, smallpox, measles and influenza are well recognized diseases in which viral vaccines have proven effective. In general, however, viral vaccines have had only a moderate success in animal prophylaxis. Each vaccine acts primarily against a specific virus and is not heterophilic in the protection it offers. Hence, vaccines have not provided a practical solution against the wide array of infectious viruses, even where limited, as for example, to respiratory viruses alone.
One approach to the control of virus-related diseases and, particularly to the spread of such virus diseases, has been to search for medicinal agents or chemotherapeutic agents which are capable of inhibiting the growth of viruses, thereby preventing the spread of disease and preventing further damage to cells and tissues of the animal host which have not as yet been infected. Heretofore, only a limited number of virus infections such as smallpox, Asian influenza, and herpes keratitis have been prevented by chemical antiviral agents. Sulfonamides and antibiotics, which have revolutionized the treatment of bacterial infections, have substantially no effect upon virus infections. Certain infections caused by large viruses, such as lymphogranuloma venereum, psittacosis and trachoma have been successfully treated using antibiotics and sulfa drugs. However, the majority of virus infections have not been responsive to attack by chemotherapeutic agents. Thus, it can be seen that there is a need for new chemotherapeutic agents which are effective against a broad range of virus diseases, and which at the same time, are non-toxic to the host.
As a result of a long series of investigations, applicants have discovered a novel class of 2,7-bis-basic fluorenes, 2,7-bis-basic fluoren-9-ols and 2,7-bis-basic fluoren-9-ones which are particularly useful antiviral agents. These compounds are effective against a wide spectrum of virus infections and are useful in treating such infections both prophylactically and therapeutically.
Applicants' copending application, Ser. No. 23,468, filed Mar. 27, 1970, whose counterpart has been published as Belgium Patent No. 764,870 represents the closest art known to applicants and discloses ketones of fluorene useful as antiviral agents. In addition the 2,7-bis-basic ketones of fluorene, which are disclosed as preferred compounds therein, further serve as starting materials for the preparation of some of the compounds of the present invention. To applicants' knowledge the compounds described and claimed herein are novel compounds which have not been previously described nor reported in the literature. Furthermore, to applicants' knowledge no aromatic bis-oximes or bis-dioximes have heretofore been reported to have antiviral activity. The compounds of the present invention possess a wide spectrum of antiviral activity in varying degrees which could not have been predicted from a knowledge of the present state of the art.